Paired and Unpaired Deep Generative Models on Multimodal Retinal Image Reconstruction

[Abstract] This work explores the use of paired and unpaired data for training deep neural networks in the multimodal reconstruction of retinal images. Particularly, we focus on the reconstruction of fluorescein angiography from retinography, which are two complementary representations of the eye fundus. The performed experiments allow to compare the paired and unpaired alternatives.Instituto de Salud Carlos III; DTS18/00136Ministerio de Ciencia, Innovación y Universidades; DPI2015-69948-RMinisterio de Ciencia, Innovación y Universidades; RTI2018-095894-B-I00Xunta de Galicia; ED431G/01Xunta de Galicia; ED431C 2016-047Xunta de Galicia; ED481A-2017/328

Self-Supervised Multimodal Reconstruction Pre-training for Retinal Computer-Aided Diagnosis

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] Computer-aided diagnosis using retinal fundus images is crucial for the early detection of many ocular and systemic diseases. Nowadays, deep learning-based approaches are commonly used for this purpose. However, training deep neural networks usually requires a large amount of annotated data, which is not always available. In practice, this issue is commonly mitigated with different techniques, such as data augmentation or transfer learning. Nevertheless, the latter is typically faced using networks that were pre-trained on additional annotated data. An emerging alternative to the traditional transfer learning source tasks is the use of self-supervised tasks that do not require manually annotated data for training. In that regard, we propose a novel self-supervised visual learning strategy for improving the retinal computer-aided diagnosis systems using unlabeled multimodal data. In particular, we explore the use of a multimodal reconstruction task between complementary retinal imaging modalities. This allows to take advantage of existent unlabeled multimodal data in the medical domain, improving the diagnosis of different ocular diseases with additional domain-specific knowledge that does not rely on manual annotation. To validate and analyze the proposed approach, we performed several experiments aiming at the diagnosis of different diseases, including two of the most prevalent impairing ocular disorders: glaucoma and age-related macular degeneration. Additionally, the advantages of the proposed approach are clearly demonstrated in the comparisons that we perform against both the common fully-supervised approaches in the literature as well as current self-supervised alternatives for retinal computer-aided diagnosis. In general, the results show a satisfactory performance of our proposal, which improves existing alternatives by leveraging the unlabeled multimodal visual data that is commonly available in the medical field.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project; Ministerio de Ciencia e Innovación, Government of Spain, through the RTI2018-095894-B-I00 and PID2019-108435RB-I00 research projects; Xunta de Galicia and the European Social Fund (ESF) of the EU through the predoctoral grant contract ref. ED481A-2017/328; Consellería de Cultura, Educación e Universidade, Xunta de Galicia, through Grupos de Referencia Competitiva, grant ref. ED431C 2020/24. CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia , through the ERDF (80%) and Secretaría Xeral de Universidades (20%)Xunta de Galicia; ED431C 2020/24Xunta de Galicia; ED431G 2019/01Xunta de Galicia; ED481A-2017/32

End-To-End Multi-Task Learning for Simultaneous Optic Disc and Cup Segmentation and Glaucoma Classification in Eye Fundus Images

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] The automated analysis of eye fundus images is crucial towards facilitating the screening and early diagnosis of glaucoma. Nowadays, there are two common alternatives for the diagnosis of this disease using deep neural networks. One is the segmentation of the optic disc and cup followed by the morphological analysis of these structures. The other is to directly address the diagnosis as an image classification task. The segmentation approach presents the advantage of using pixel-level labels with precise morphological information for training. However, while this detailed training feedback is not available for the classification approach, in this case the image-level labels may allow the discovery of additional non-morphological cues that are also relevant for the diagnosis. In this work, we propose a novel multi-task approach for the simultaneous classification of glaucoma and segmentation of the optic disc and cup. This approach can improve the overall performance by taking advantage of both pixel-level and image-level labels during the network training. Additionally, the segmentation maps that are predicted together with the diagnosis allow the extraction of relevant biomarkers such as the cup-to-disc ratio. The proposed methodology presents two relevant technical novelties. First, a network architecture for simultaneous segmentation and classification that increases the number of shared parameters between both tasks. Second, a multi-adaptive optimization strategy that ensures that both tasks contribute similarly to the parameter updates during training, avoiding the use of loss weighting hyperparameters. To validate our proposal, an exhaustive experimentation was performed on the public REFUGE and DRISHTI-GS datasets. The results show that our proposal outperforms comparable multi-task baselines and is highly competitive with existing state-of-the-art approaches. Additionally, the provided ablation study shows that both the network architecture and the optimization approach are independently advantageous for multi-task learning.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project; Ministerio de Ciencia e Innovación, Government of Spain, through the RTI2018-095894-B-I00 and PID2019-108435RB-I00 research projects; Axencia Galega de Innovación (GAIN), Spain, Xunta de Galicia, through grant ref. IN845D 2020/38; Xunta de Galicia and the European Social Fund (ESF) of the EU through the predoctoral contract ref. ED481A-2017/328; Consellería de Cultura, Educación e Universidade, Xunta de Galicia, Spain, through Grupos de Referencia Competitiva, grant ref. ED431C 2020/24. CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from Consellería de Cultura, Educación e Universidade, Xunta de Galicia, Spain, through the ERDF (80%) and Secretaría Xeral de Universidades (20%), Spain . Funding for open access charge: Universidade da Coruña/CISUG, Spain.Xunta de Galicia; IN845D 2020/38Xunta de Galicia; ED481A-2017/328Xunta de Galicia; ED431C 2020/24Xunta de Galicia; ED431G 2019/0

Learning the Retinal Anatomy From Scarce Annotated Data Using Self-Supervised Multimodal Reconstruction

[Abstract] Deep learning is becoming the reference paradigm for approaching many computer vision problems. Nevertheless, the training of deep neural networks typically requires a significantly large amount of annotated data, which is not always available. A proven approach to alleviate the scarcity of annotated data is transfer learning. However, in practice, the use of this technique typically relies on the availability of additional annotations, either from the same or natural domain. We propose a novel alternative that allows to apply transfer learning from unlabelled data of the same domain, which consists in the use of a multimodal reconstruction task. A neural network trained to generate one image modality from another must learn relevant patterns from the images to successfully solve the task. These learned patterns can then be used to solve additional tasks in the same domain, reducing the necessity of a large amount of annotated data. In this work, we apply the described idea to the localization and segmentation of the most important anatomical structures of the eye fundus in retinography. The objective is to reduce the amount of annotated data that is required to solve the different tasks using deep neural networks. For that purpose, a neural network is pre-trained using the self-supervised multimodal reconstruction of fluorescein angiography from retinography. Then, the network is fine-tuned on the different target tasks performed on the retinography. The obtained results demonstrate that the proposed self-supervised transfer learning strategy leads to state-of-the-art performance in all the studied tasks with a significant reduction of the required annotations.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project, and by Ministerio de Economía, Industria y Competitividad, Government of Spain, through the DPI2015-69948-R research project. The authors of this work also receive financial support from the ERDF and Xunta de Galicia (Spain) through Grupo de Referencia Competitiva, ref. ED431C 2016-047, and from the European Social Fund (ESF) of the EU and Xunta de Galicia (Spain) through the predoctoral grant contract ref. ED481A-2017/328. CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia (Spain) , through the ERDF (80%) and Secretaría Xeral de Universidades (20%)Xunta de Galicia; ED431C 2016-047Xunta de Galicia ; ED481A-2017/328Xunta de Galicia; ED431G 2019/0

Self-Supervised Multimodal Reconstruction of Retinal Images Over Paired Datasets

[Abstract] Data scarcity represents an important constraint for the training of deep neural networks in medical imaging. Medical image labeling, especially if pixel-level annotations are required, is an expensive task that needs expert intervention and usually results in a reduced number of annotated samples. In contrast, extensive amounts of unlabeled data are produced in the daily clinical practice, including paired multimodal images from patients that were subjected to multiple imaging tests. This work proposes a novel self-supervised multimodal reconstruction task that takes advantage of this unlabeled multimodal data for learning about the domain without human supervision. Paired multimodal data is a rich source of clinical information that can be naturally exploited by trying to estimate one image modality from others. This multimodal reconstruction requires the recognition of domain-specific patterns that can be used to complement the training of image analysis tasks in the same domain for which annotated data is scarce. In this work, a set of experiments is performed using a multimodal setting of retinography and fluorescein angiography pairs that offer complementary information about the eye fundus. The evaluations performed on different public datasets, which include pathological and healthy data samples, demonstrate that a network trained for self-supervised multimodal reconstruction of angiography from retinography achieves unsupervised recognition of important retinal structures. These results indicate that the proposed self-supervised task provides relevant cues for image analysis tasks in the same domain.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project, and by Ministerio de Economía, Industria y Competitividad, Government of Spain, through the DPI2015-69948-R research project. The authors of this work also receive financial support from the ERDF and Xunta de Galicia through Grupo de Referencia Competitiva, Ref. ED431C 2016-047, and from the European Social Fund (ESF) of the EU and Xunta de Galicia through the predoctoral grant contract Ref. ED481A-2017/328. CITIC, Centro de Investigación de Galicia Ref. ED431G 2019/01, receives financial support from Consellería de Educación, Universidade e Formación Profesional, Xunta de Galicia, through the ERDF (80%) and Secretaría Xeral de Universidades (20%)Xunta de Galicia; ED431C 2016-047Xunta de Galicia; ED481A-2017/328Xunta de Galicia; ED431G 2019/0

Retinal Microaneurysms Detection Using Adversarial Pre-training With Unlabeled Multimodal Images

Financiado para publicación en acceso aberto: Universidade da Coruña/CISUG[Abstract] The detection of retinal microaneurysms is crucial for the early detection of important diseases such as diabetic retinopathy. However, the detection of these lesions in retinography, the most widely available retinal imaging modality, remains a very challenging task. This is mainly due to the tiny size and low contrast of the microaneurysms in the images. Consequently, the automated detection of microaneurysms usually relies on extensive ad-hoc processing. In this regard, although microaneurysms can be more easily detected using fluorescein angiography, this alternative imaging modality is invasive and not adequate for regular preventive screening. In this work, we propose a novel deep learning methodology that takes advantage of unlabeled multimodal image pairs for improving the detection of microaneurysms in retinography. In particular, we propose a novel adversarial multimodal pre-training consisting in the prediction of fluorescein angiography from retinography using generative adversarial networks. This pre-training allows learning about the retina and the microaneurysms without any manually annotated data. Additionally, we also propose to approach the microaneurysms detection as a heatmap regression, which allows an efficient detection and precise localization of multiple microaneurysms. To validate and analyze the proposed methodology, we perform an exhaustive experimentation on different public datasets. Additionally, we provide relevant comparisons against different state-of-the-art approaches. The results show a satisfactory performance of the proposal, achieving an Average Precision of 64.90%, 31.36%, and 33.55% in the E-Ophtha, ROC, and DDR public datasets. Overall, the proposed approach outperforms existing deep learning alternatives while providing a more straightforward detection method that can be effectively applied to raw unprocessed retinal images.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project; Ministerio de Ciencia e Innovación, Government of Spain, through the RTI2018-095894-B-I00 and PID2019-108435RB-I00 research projects; Xunta de Galicia, Spain and the European Social Fund (ESF) of the EU through the predoctoral grant contract ref. ED481A-2017/328; Consellería de Cultura, Educación e Universidade, Xunta de Galicia, through Grupos de Referencia Competitiva, grant ref. ED431C 2020/24. CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from Consellería de Cultura, Educación e Universidade, Xunta de Galicia , through the ERDF (80%) and Secretaría Xeral de Universidades (20%). Funding for open access charge: Universidade da Coruña/CISUGXunta de Galicia; ED481A-2017/328Xunta de Galicia; ED431C 2020/24Xunta de Galicia; ED431G 2019/0

Heartbeat classification fusing temporal and morphological information of ECGs via ensemble of classifiers

©2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/. This version of the article: Mondéjar-Guerra, V., Novo, J., Rouco, J., Penedo, M. G., & Ortega, M. (2019). “Heartbeat classification fusing temporal and morphological information of ECGs via ensemble of classifiers” has been accepted for publication in Biomedical Signal Processing and Control, 47, 41–48. The Version of Record is available online at: https://doi.org/10.1016/j.bspc.2018.08.007.[Abstract]: A method for the automatic classification of electrocardiograms (ECG) based on the combination of multiple Support Vector Machines (SVMs) is presented in this work. The method relies on the time intervals between consequent beats and their morphology for the ECG characterisation. Different descriptors based on wavelets, local binary patterns (LBP), higher order statistics (HOS) and several amplitude values were employed. Instead of concatenating all these features to feed a single SVM model, we propose to train specific SVM models for each type of feature. In order to obtain the final prediction, the decisions of the different models are combined with the product, sum, and majority rules. The designed methodology approaches are tested on the public MIT-BIH arrhythmia database, classifying four kinds of abnormal and normal beats. Our approach based on an ensemble of SVMs offered a satisfactory performance, improving the results when compared to a single SVM model using the same features. Additionally, our approach also showed better results in comparison with previous machine learning approaches of the state-of-the-art.This work was partially supported by the Research Project RTC-2016-5143-1, financed by the Spanish Ministry of Economy, Industry and Competitiveness and the European Regional Development Fund (ERDF). Also, this work has received financial support from the ERDF and the Xunta de Galicia, Centro singular de investigación de Galicia accreditation 2016–2019, Ref. ED431G/01; and Grupos de Referencia Competitiva, Ref. ED431C 2016-047.Xunta de Galicia; ED431G/01Xunta de Galicia; ED431C 2016-04

Comprehensive analysis of clinical data for COVID-19 outcome estimation with machine learning models

Funding for open access charge: Universidade da Coruña/CISUG.[Abstract]: COVID-19 is a global threat for the healthcare systems due to the rapid spread of the pathogen that causes it. In such situation, the clinicians must take important decisions, in an environment where medical resources can be insufficient. In this task, the computer-aided diagnosis systems can be very useful not only in the task of supporting the clinical decisions but also to perform relevant analyses, allowing them to understand better the disease and the factors that can identify the high risk patients. For those purposes, in this work, we use several machine learning algorithms to estimate the outcome of COVID-19 patients given their clinical information. Particularly, we perform 2 different studies: the first one estimates whether the patient is at low or at high risk of death whereas the second estimates if the patient needs hospitalization or not. The results of the analyses of this work show the most relevant features for each studied scenario, as well as the classification performance of the considered machine learning models. In particular, the XGBoost algorithm is able to estimate the need for hospitalization of a patient with an AUC-ROC of 0.8415± 0.0217 while it can also estimate the risk of death with an AUC-ROC of 0.7992±0.0104. Results have demonstrated the great potential of the proposal to determine those patients that need a greater amount of medical resources for being at a higher risk. This provides the healthcare services with a tool to better manage their resources.Xunta de Galicia; ED481A 2021/196Xunta de Galicia; ED431C 2020/24Xunta de Galicia; IN845D 2020/38Xunta de Galicia; ED431G 2019/01This research was funded by ISCIII, Government of Spain, DTS18/00136 research project; Ministerio de Ciencia e Innovación y Universidades, Government of Spain, RTI2018-095894-B-I00 research project; Ministerio de Ciencia e Innovación, Government of Spain through the research project with reference PID2019-108435RB-I00; CCEU, Xunta de Galicia through the predoctoral grant contract ref. ED481A 2021/196; and Grupos de Referencia Competitiva, grant ref. ED431C 2020/24; Axencia Galega de Innovación (GAIN), Xunta de Galicia, grant ref. IN845D 2020/38; CITIC, Centro de Investigación de Galicia ref. ED431G 2019/01, receives financial support from CCEU, Xunta de Galicia , through the ERDF (80%) and Secretaría Xeral de Universidades (20%). Funding for open access charge: Universidade da Coruña/CISUG

Deep multi-instance heatmap regression for the detection of retinal vessel crossings and bifurcations in eye fundus images

©2020. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/. This version of the article: Hervella, Á. S., Rouco, J., Novo, J., Penedo, M. G., & Ortega, M. (2020). “Deep multi-instance heatmap regression for the detection of retinal vessel crossings and bifurcations in eye fundus images” has been accepted for publication in Computer Methods and Programs in Biomedicine, 186(105201), 105201. The Version of Record is available online at: https://doi.org/10.1016/j.cmpb.2019.105201.[Abstract]: Background and objectives:The analysis of the retinal vasculature plays an important role in the diagnosis of many ocular and systemic diseases. In this context, the accurate detection of the vessel crossings and bifurcations is an important requirement for the automated extraction of relevant biomarkers. In that regard, we propose a novel approach that addresses the simultaneous detection of vessel crossings and bifurcations in eye fundus images. Method: We propose to formulate the detection of vessel crossings and bifurcations in eye fundus images as a multi-instance heatmap regression. In particular, a deep neural network is trained in the prediction of multi-instance heatmaps that model the likelihood of a pixel being a landmark location. This novel approach allows to make predictions using full images and integrates into a single step the detection and distinction of the vascular landmarks. Results: The proposed method is validated on two public datasets of reference that include detailed annotations for vessel crossings and bifurcations in eye fundus images. The conducted experiments evidence that the proposed method offers a satisfactory performance. In particular, the proposed method achieves 74.23% and 70.90% F-score for the detection of crossings and bifurcations, respectively, in color fundus images. Furthermore, the proposed method outperforms previous works by a significant margin. Conclusions: The proposed multi-instance heatmap regression allows to successfully exploit the potential of modern deep learning algorithms for the simultaneous detection of retinal vessel crossings and bifurcations. Consequently, this results in a significant improvement over previous methods, which will further facilitate the automated analysis of the retinal vasculature in many pathological conditions.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project, and by Ministerio de Ciencia, Innovación y Universidades, Government of Spain, through the DPI2015-69948-R and RTI2018-095894-B-I00 research projects. The authors of this work also receive financial support from the ERDF and European Social Fund (ESF) of the EU, and Xunta de Galicia through Centro Singular de Investigación de Galicia, accreditation 2016–2019, ref. ED431G/01, Grupo de Referencia Competitiva, ref. ED431C 2016-047, and the predoctoral grant contract ref. ED481A-2017/328.Xunta de Galicia; ED431G/01Xunta de Galicia; ED431C 2016-047Xunta de Galicia; ED481A-2017/32

Joint Optic Disc and Cup Segmentation Using Self-Supervised Multimodal Reconstruction Pre-Training

[Abstract] The analysis of the optic disc and cup in retinal images is important for the early diagnosis of glaucoma. In order to improve the joint segmentation of these relevant retinal structures, we propose a novel approach applying the self-supervised multimodal reconstruction of retinal images as pre-training for deep neural networks. The proposed approach is evaluated on different public datasets. The obtained results indicate that the self-supervised multimodal reconstruction pre-training improves the performance of the segmentation. Thus, the proposed approach presents a great potential for also improving the interpretable diagnosis of glaucoma.This work is supported by Instituto de Salud Carlos III, Government of Spain, and the European Regional Development Fund (ERDF) of the European Union (EU) through the DTS18/00136 research project, and by Ministerio de Ciencia, Innovación y Universidades, Government of Spain, through the RTI2018-095894-B-I00 research project. The authors of this work also receive financial support from the ERDF, the European Social Fund (ESF) of the EU, and Xunta de Galicia through Centro de Investigación de Galicia ref. ED431G 2019/01 and the predoctoral grant contract ref. ED481A-2017/328Xunta de Galicia; ED431G 2019/01Xunta de Galicia; ED481A-2017/328